Bleeding disorders in women are an under-recognized and under-treated condition. Expert guidelines recommend screening for von Willebrand Disease (VWD) in adolescents with severe heavy menstrual bleeding (HMB). However, what is not known is the optimal VWD screening algorithm to utilize for young women with HMB. The long-term goal is to perform research that aids in expanded screening for and timely diagnosis of bleeding disorders in women, with the ultimate goal to decrease the frequency and morbidity of reproductive bleeding. The objective of this U34 application is to support refinement and planning activities for a trial comparing two screening algorithms for identifying young women with a high likelihood of VWD. The central hypothesis is that a combination of the International Society of Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) and point-of-care ferritin testing will have high specificity (?80%) in the evaluation of VWD. The rationale for this research is that earlier diagnosis of VWD can alleviate complications such as iron deficiency anemia, school and work absences, surgical or postpartum bleeding, unnecessary hysterectomy, and even mortality due to bleeding complications. Thus, the proposed research is relevant to the NHLBI's mission to develop novel strategies to prevent hemorrhagic complications. This hypothesis will be tested by pursuing two specific aims: 1) Determine clinical characteristics that predict the presence of VWD in young women with HMB; and 2) Compare the utility of two screening algorithms to identify young women with VWD. In the first aim, using PEDSnet (a longitudinal data resource combining the electronic health records of eight children's hospitals), a retrospective study will be performed of young women with HMB who have undergone laboratory evaluation for VWD to determine key historical predictors for VWD. The second aim is a randomized trial to determine the utility of a VWD screening algorithm for young women in a variety of urban and rural healthcare settings that includes the ISTH-BAT alone as compared to the ISTH-BAT with point-of- care ferritin level. The approach is innovative because it shifts the study of young women with bleeding disorders from the status quo of specialized hematology centers to primary care settings in which young women with HMB initially present. The approach requires innovation in clinical design and statistical analysis for several reasons, including 1) statistical challenges of ?big data? from electronic health records, 2) methodologic challenges of low event rates, 3) need for randomization-by-site, and 4) need for sampling strategies to ensure strong representation from rural patients and racial/ethnic minorities. Receipt of this award will yield the following expected outcomes: 1) collaboration with the NHLBI's Innovative Clinical Trial Resource to refine the trial design and analytic plan, 2) selection of study sites in urban and rural Ohio for the proposed work, and 3) submission of a UG3/UH3 application for a multi-site clinical trial. The proposed work is significant because earlier diagnosis of VWD can alleviate morbidity and mortality due to bleeding complications.